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What do we really know about ovarian cancer risk and the 'gene mutations' considered largely responsible for increasing it? The answer is quite surprising and opens up the possibility for a radical change in how we diagnosis and treat the most lethal gynecological cancer in existence.
Ovarian cancer strikes fear into the hearts of women, their families, and their doctors, alike. Risks of false positive diagnosis leading to a treatment that has been demonstrated to result in the worst outcomes of any gynecologic cancer have led the U.S. Preventive Services Task Force (USPSTF) to recommend against routine screening.
The real tragedy – largely still unacknowledged – is that ovarian cancer statistics are not transparent to the fact that five times more women without ovarian cancer end up having surgery than those with ovarian cancer, according to a 2011 JAMA retrospective study of ovarian cancer screening.
The JAMA trial of 78,216 women found that those in the intervention group who underwent annual screening for ovarian cancer (39,105) evaluating serum cancer antigen (CA-125) for 6 years and transvaginal ultrasound for 4 years, were far more likely to receive a false-positive diagnosis (3,285 women) than an accurate positive cancer diagnosis (212 women). 32.9 percent of the false positives – 1,080 women -- opted for oophorectomy surgery (surgical removal of one or both ovaries), a fact that can not fully convey the untold suffering, morbidity and decrease in lifespan they experienced as a result of these medical 'mistakes.' For instance, we know from breast cancer research that even when women receive false positive diagnoses that are soon followed by corrective cancer-free diagnoses, the negative psychosocial outcomes of the shock of false diagnosis persist for at least 3 years. [See: Hidden Dangers of Mammograms That Every Woman Should Know.]
In other words, being diagnosed and being treated for ovarian cancer is not the same as actually having it. The ovarian cancer statistics, however, do not take this into account, making the problem of 'ovarian cancer' look much larger than the problem of medical iatrogenesis itself. The fear created by this disingenuous representation of the problem, further amplifies the fear that drives even more presumably healthy women into overdiagnosis and overtreatment, feeding this vicious cycle – a cycle occurring on an epidemic scale with other screen-detected 'cancers,' such as breast, prostate, lung and thyroid. [See: Millions Wrongly Treated for 'Cancer,' National Cancer Institute Panel Confirms.]
Presumably, family history and so-called BRCA gene status are the best method to determine your risk. And today, with high profile figures like Angelina Jolie removing her breasts and soon her ovaries due to what she is being told is her extremely elevated risk associated with her family history and BRCA status, millions around the world are now looking at Jolie's decision as a viable method to 'take back control' of their health vis-à-vis cancer. The Orwellian result? 'Prevention' is being equated with the removal of non-diseased organs.
But are BRCA mutations – technically, BRCA single nucleotide polymorphisms (SNPs), of which there are hundreds– really the primary drivers of ovarian cancer risk? Is being born with 'bad genes,' and having close family members with a history of gynecological cancer, alone enough to make an informed choice?
Inherited BRCA Gene 'Mutations' Alone Do Not Determine Your Cancer Risk
The answer is a resounding NO. BRCA mutation status is only one factor to consider. Every man and woman has the BRCA1 and 2 genes within their genome, and regardless of whether they were born with a variant that renders the cancer-protective BRCA protein dysfunctional or inactive (i.e. germline mutations), or came to acquire it later in life as a result of genetic processes we do not fully understand (i.e. somatic mutation), BRCA genes in susceptible tissues, e.g. breast, ovary, prostate, can be deactivated through factors beyond the control of the genes (epigenetic factors), such as through viral infection (SV-40, Epstein-Barr virus), chemical exposures, nutritional factors, and even mind-body processes that have downstream physiological effects that directly modulate the structure and function of our genome and epigenome. In fact, whether a BRCA gene is rendered dysfunctional through an inborn 'mutation' or from the 'outside in,' through the silencing of the gene (hypermethylation of the promote region of the gene), the result is the same as far as the cell phenotype and BRCA protein production is concerned. This means that risk can not be calculated accurately without taking into account both genetic and epigenetic factors, with the crucial difference being that epigenetic changes to BRCA such as hypermethylation of the gene is at least theoretically partially reversible and/or preventable through behavioral, nutritional, environmental and lifestyle changes.
There is a prevailing belief in conventional medicine and among the lay public, today, that if you possess a BRCA1 mutation, you are fated to develop cancer. But inborn or developed BRCA1 variations are so complex, with literally hundreds identified, that there are few studies that have even attempted to identify and validate the risk associated with each variant. Bunched together under the umbrella concept of a 'BRCA gene mutation,' the reality is that anyone can develop BRCA1 or BRCA2 dysfunction in their lifetime through chemical and infectious exposures and nutritional incompatibilities and deficiencies, such that the resulting gene-silenting effect (methylation) is the same: the BRCA genes are altered within the cells, producing changes consistent with the appearance of pathology in a screen-detected lesion or tumor.
Indeed, a recent study published in Tumour Biology titled, "BRCA1 promoter hypermethylation and protein expression in ovarian carcinoma—an Indian study," found that BRCA1 gene silencing through promoter region hypermethylation were frequent events in ovarian cancer. The frequency of BRCA1 gene silencing in epithelial ovarian carcinoma (EOC) was 51.2% and 57% in low malignant potential tumors (LMP). They found that BRCA1 protein expression (remember, BRCA proteins protect against DNA damage and tumor initiation and promotion) was significantly lower in EOCs, and that the lack of protein expression correlated with tumor grade and type, and the methylation status correlated with reduced BRCA1 expression. Remarkably, they found that benign tumors and normal ovarian tissue showed no methylation of the BRCA1 gene -- indicating that epigenetic methylation (as opposed to inherited gene defects) is also a primary driver of ovarian cancer malignancy.
Clearly, this indicates that factors outside the primary DNA sequences that constitute the BRCA genes themselves play a vitally important role in determining if these genes function correctly. This shifts the focus to the avoidable causes of BRCA gene silencing, indicating that cancer risk is not a juggernaut force of lethality buried within the destiny of genes; rather, that we have a hand to play in the process.
Why Do BRCA Gene Mutations Improve Ovarian Cancer Survival Outcomes?
Furthermore, the published literature shows that having a BRCA1/BRCA2 mutation actually confers improved survival from ovarian cancer. A recent meta-analysis found that of 35 evaluable studies, 23 identified BRCA dysfunction status as a favorable prognostic factor. The commonly agreed upon explanation for this counterintuitive finding is that platinum-based chemotherapy is more effective against ovarian cancer cells that have dysfunctional DNA repair mechanisms associated with a BRCA mutation. The problem, however, is that the class of chemotherapy compounds that exert genotoxicity as their primarily mechanism of action also result in widespread collateral damage to healthy tissue, as well as enriching the chemoresistant cancer stem cell subpopulation within a tumor, leading to in increase in the malignancy of the cancer tissue that can not be de-bulked/destroyed – the result of which is the recurrence of more aggressive, life-threatening cancers, despite the slight improvement in survival offered initially from the treatment (stage 4 ovarian cancer only has a 5-year survival rate of 18%).
While not yet sufficiently explored, relatively non-toxic botanical extracts such as curcumin, resveratrol and green tea, and several dozen others (including frankincense), exert anti-ovarian cancer properties, while often exhibiting the property of selective cytoxicity, targeting ovarian cancer cells for epigenetic modifications leading to arrest of the cell cycle and cell death, without harming non-cancerous cells. It is possible that BRCA dysfunction, therefore, may also respond exceptionally well to plant-based therapies, putting a different spin on the prevalent 'breast' and 'ovarian' cancer gene meme, and perhaps conferring a survival advantage if only researchers would make effectiveness and safety a priority over developing proprietary formulations that are eligible for patent approval. [See: Why the Law Forbids The Medicinal Use of Natural Substances]
Moving Beyond the 'Mutated Genes Cause Cancer' Paradigm
Clearly, given these considerations, we must move beyond the fatalistic 'breast cancer' or 'ovarian cancer' gene (BRCA) memeplex and recognize the factors that we can control are at least as important as those we cannot (i.e. germline DNA sequences). For instance, we know that not only can certain petrochemicals 'knock out' BRCA gene function, but certain natural food components like reseveratrol found in grapes and peanuts, can protect the BRCA gene against this exposure. For a detailed explanation of this research read our article 'Beyond the 'Breast Cancer' Gene (BRCA): Why Food is Your Medicine.'
Medical science is going through massive internal shifts today, still trying to catch up almost a decade later to the fact that we are in the post-genomic era, and the sequencing of genes themselves will not produce the much anticipated holy grail of molecular biology, and by implication radical improvements in the cure of disease. We, as a society, are being forced to consider the vital importance of our lifestyle in the complexity of modern chronic illness. Unfortunately, lifestyle is still a neglected and dismissed concept in the halls of America's medical schools. The evidence speaks to the dangerous reductionism of this paradigm, particularly in the realm of women's health and the protection of the female body from the aggression of an ill-informed establishment. Wrest back control and shed the fear, which, in and of itself, may be medicine's most toxic intervention.
 U.S. Preventive Services Task Force Ovarian Cancer Screening Recommendations. 2012
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